Abstract
Objective Chronic unpredictable stress (CUS) can influence the risk and progression of cancer through increased oxidative stress. Quercetin (QU), a phytochemical found in daily foods, has been extensively studied as a chemopreventive agent against various types of cancers. Our aim was to investigate the role of CUS on the efficacy of QU against DMBA+TPA (7, 12-dimethylbenz (a) anthracene+12-O-Tetradecanoylphorbol-13-acetate)-induced skin carcinogenesis. Methods Eighty-four adult male Swiss albino mice were randomly divided into seven groups (12 mice/group) based on different treatments and killed after 16 weeks. Blood and skin tissues were collected for biochemical estimations, DNA damage analysis and fluorescent studies. Results Group receiving oral administration of QU together with DMBA+TPA showed significantly elevated antioxidant status accompanied by decreased lipid peroxidation and DNA damage, reduced tumor incidence, burden and yield as compared to the groups treated with DMBA+TPA or CUS+DMBA+TPA. However, the introduction of animals to CUS prior to oral QU administration decreased its efficacy as indicated by the declined antioxidant status along with increased lipid peroxidation, DNA damage, tumor incidence, burden and yield. The results of fluorescent spectral analysis also corroborated the above findings. Conclusion CUS not only increased the severity of carcinogenesis, but also suppressed the antioxidant and chemopreventive potential of QU through induction of oxidative stress, thereby emphasizing the need to manage or reduce stress during chemoprevention/chemotherapy.